Alobaid Meshal A, Richards Sarah-Jane, Alexander Morgan R, Gibson Matthew I, Ghaemmaghami Amir M
Immunology & Immuno-bioengineering, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
Biology, Immunology, American International University, Al-Jahra, Saad Al Abdullah, Kuwait.
Mater Today Bio. 2024 Nov 27;29:101371. doi: 10.1016/j.mtbio.2024.101371. eCollection 2024 Dec.
Dendritic cells (DCs) have emerged as a promising target for drug delivery and immune modulation due to their pivotal role in initiating the adaptive immune response. Gold nanoparticles (AuNPs) have garnered interest as a platform for targeted drug delivery due to their biocompatibility, low toxicity and precise control over size, morphology and surface functionalization. Our investigation aimed to elucidate the intracellular uptake and trafficking of AuNPs coated with different combinations of monosaccharides (mannose, galactose, and fucose) in DCs. We used 30 unique polymer-tethered monosaccharide combinations to coat 16 nm diameter spherical gold nanoparticles and investigated their effect on DCs phenotype, uptake, and intracellular trafficking. DCs internalized AuNPs coated with 100 % fucose, 100 % mannose, 90 % mannose +10 % galactose, and 80 % mannose +20 % galactose with highest efficiency. Flow cytometry analysis indicated that 100 % fucose-coated AuNPs showed increased lysosomal and endosomal contents compared to other conditions and uncoated AuNPs. Imaging flow cytometry further demonstrated that 100 % fucose-coated AuNPs had enhanced co-localization with lysosomes, while 100 % mannose-coated AuNPs exhibited higher co-localization with endosomes. Furthermore, our data showed that the uptake of carbohydrate-coated AuNPs predominantly occurred through receptor-mediated endocytosis, as evidenced by a marked reduction of uptake upon treatment of DCs with methyl-β-cyclodextrins, known to disrupt receptor-mediated endocytosis. These findings highlight the utility of carbohydrate coatings to enable more targeted delivery of nanoparticles and their payload to distinct intracellular compartments in immune cells with potential applications in drug delivery and immunotherapy.
由于树突状细胞(DCs)在启动适应性免疫反应中起关键作用,它们已成为药物递送和免疫调节的一个有前景的靶点。金纳米颗粒(AuNPs)因其生物相容性、低毒性以及对尺寸、形态和表面功能化的精确控制,已成为靶向药物递送的一个受关注的平台。我们的研究旨在阐明用不同单糖(甘露糖、半乳糖和岩藻糖)组合包被的AuNPs在DCs中的细胞内摄取和转运情况。我们使用30种独特的聚合物连接单糖组合来包被直径为16纳米的球形金纳米颗粒,并研究它们对DCs表型、摄取和细胞内转运的影响。DCs对用100%岩藻糖、100%甘露糖、90%甘露糖 + 10%半乳糖和80%甘露糖 + 20%半乳糖包被的AuNPs摄取效率最高。流式细胞术分析表明,与其他条件和未包被的AuNPs相比,100%岩藻糖包被的AuNPs显示溶酶体和内体含量增加。成像流式细胞术进一步证明,100%岩藻糖包被的AuNPs与溶酶体的共定位增强,而100%甘露糖包被的AuNPs与内体的共定位更高。此外,我们的数据表明,碳水化合物包被的AuNPs的摄取主要通过受体介导的内吞作用发生,用甲基-β-环糊精处理DCs后摄取显著减少证明了这一点,已知甲基-β-环糊精会破坏受体介导的内吞作用。这些发现突出了碳水化合物包被在使纳米颗粒及其有效载荷更有针对性地递送至免疫细胞中不同细胞内区室方面的效用,在药物递送和免疫治疗中具有潜在应用。
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